Metabolic syndrome (MetS) is a cluster of interrelated and co-occurring metabolic disorders, including abdominal obesity, hyperglycemia, dyslipidemia, the reduced high-density lipoprotein (HDL) cholesterol, and/or hypertension. Cardiovascular diseases are the leading causes of death and disability in metabolic syndrome. Each component of MetS is an independent risk factor for cardiovascular diseases, and the combination of these factors can increase the incidence and severity of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure, with atherosclerosis being the primary cause of cardiovascular-related death in MetS. The specific pathogenic mechanism in the occurrence and development of atherosclerosis in MetS is still not fully understood. An increasing number of studies have shown that the purinergic signaling pathway plays a significant role in atherosclerosis. ATP and ADP, key signaling molecules in the purinergic signaling pathway, are not only involved in cellular energy metabolism but also activate the purinergic signaling pathway by binding to P1 and P2 purinergic receptors (P1R and P2R), regulating vascular contraction and relaxation, and inhibiting platelet aggregation. Purinergic signaling can act as both a promoter and a resistance factor in the formation of atherosclerosis, depending on the receptor subtype and downstream signaling network. This review summarizes the specific roles and mechanisms of the purinergic signaling network in MetS-related atherosclerosis and analyzes the clinical application of targeting the purinergic signaling pathway, providing a theoretical basis and innovative ideas for basic research and clinical treatment in this field.

BACKGROUND Suicide constitutes the second leading cause of death among adolescents globally and represents a critical public health concern. The neural mechanisms underlying suicidal behavior in adolescents with major depressive disorder (MDD) remain poorly understood. Aberrant resting-state functional connectivity (rsFC) in the amygdala, a key region implicated in emotional regulation and threat detection, is strongly implicated in depression and suicidal behavior. AIM To investigate rsFC alterations between amygdala subregions and whole-brain networks in adolescent patients with depression and suicide attempts. METHODS Resting-state functional magnetic resonance imaging data were acquired from 32 adolescents with MDD and suicide attempts (sMDD) group, 33 adolescents with MDD but without suicide attempts (nsMDD) group, and 34 demographically matched healthy control (HC) group, with the lateral and medial amygdala (MeA) defined as regions of interest. The rsFC patterns of amygdala subregions were compared across the three groups, and associations between aberrant rsFC values and clinical symptom severity scores were examined. RESULTS Compared with the nsMDD group, the sMDD group exhibited reduced rsFC between the right lateral amygdala (LA) and the right inferior occipital gyrus as well as the left middle occipital gyrus. Compared with the HC group, the abnormal brain regions of rsFC in the sMDD group and nsMDD group involve the parahippocampal gyrus (PHG) and fusiform gyrus. In the sMDD group, right MeA and right temporal pole: Superior temporal gyrus rsFC value negatively correlated with the Rosenberg Self-Esteem Scale scores (r = -0.409, P = 0.025), while left LA and right PHG rsFC value positively correlated with the Adolescent Self-Rating Life Events Checklist interpersonal relationship scores (r = 0.372, P = 0.043). CONCLUSION Aberrant rsFC changes between amygdala subregions and these brain regions provide novel insights into the underlying neural mechanisms of suicide attempts in adolescents with MDD.

BACKGROUND Ischemic stroke is one of the leading global causes of disability and death. Despite advances in modern medical technology that improve acute treatment and rehabilitation measures, post-stroke anxiety and depression (PSD) do not receive sufficient attention. AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice. METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024. Based on assessments using the Hamilton Rating Scale for Anxiety (HAMA) and Hamilton Rating Scale for Depression (HAMD) at 2 weeks (± 3 days) post-stroke, patients were classified into the PSD group (HAMA ≥ 7 and/or HAMD ≥ 7) and the non-PSD group (HAMA < 7 and HAMD < 7). Observation indicators included psychological assessment, demographic and clinical characteristics, stroke-related clinical indicators, neuroimaging assessments, and laboratory biomarkers. Multivariate logistic regression analysis was used to identify independent risk factors for PSD, and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers. RESULTS Of the 112 patients, 46 (41.1%) were diagnosed with PSD. Multivariate analysis identified five independent risk factors: Female gender [Odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.56-3.45], history of mental disorders prior to stroke (OR = 3.17, 95%CI: 1.89-5.32), infarct location in the frontal lobe or limbic system (OR = 2.86, 95%CI: 1.73-4.71), stroke severity with National Institutes of Health Stroke Scale ≥ 8 at admission (OR = 2.54, 95%CI: 1.62-3.99), and low social support (Social Support Rating Scale < 35, OR = 2.18, 95%CI: 1.42-3.36). Subgroup analysis showed that depression patients more commonly had left hemisphere lesions (68.4% vs 45.2%), while anxiety patients more frequently presented with right hemisphere lesions (59.5% vs 39.5%). The PSD group exhibited larger infarct volumes (8.7 cm3 vs 5.3 cm3), more severe white matter hyperintensities, and more pronounced frontal lobe atrophy. Analysis of inflammatory markers showed significantly elevated levels of interleukin-6 (7.8 pg/mL vs 4.5 pg/mL) and tumor necrosis factor-alpha (15.6 pg/mL vs 9.8 pg/mL) in the PSD group, while hypothalamic-pituitary-adrenal axis function assessment revealed higher cortisol levels (386.5 ± 92.3 nmol/L vs 328.7 ± 75.6 nmol/L) and flattened diurnal rhythm in the PSD group. CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry, neuroinflammatory responses, and dysfunction of the hypothalamic-pituitary-adrenal axis.

Breast cancer is the most common malignancy among women and remains the leading cause of cancer-related death in this population. Radionuclide-based diagnostic and therapeutic approaches have emerged as effective and low-risk strategies for management of breast cancer. This study aimed to evaluate the diagnostic performance of [68Ga]Ga-FAP-2286 PET/CT compared with [18F]FDG PET/CT, and to provide a preliminary assessment of the clinical potential of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy in patients with advanced breast cancer. A total of twenty patients with clinically suspected recurrent or metastatic breast cancer were prospectively enrolled. All participants underwent both [18F]FDG PET/CT and [68Ga]Ga-FAP-2286 PET/CT imaging within one week. The positivity rate of lesions, maximum standardized uptake value (SUVmax), and tumor-to-background ratio (TBR) were compared between the two imaging modalities across different involved organs. In addition, four patients received a single cycle of [¹⁷⁷Lu]Lu-FAP-2286 radionuclide therapy, and were followed for 4 months to assess therapeutic response and safety. The total number of lesions detected by [68Ga]Ga-FAP-2286 PET/CT was significantly higher than that detected by [18F]FDG PET/CT (85.4% vs. 70.5%, P < 0.001). This superiority was particularly evident for hepatic metastases (94.7% vs. 68.9%, P < 0.001) and bone metastases (85.8% vs. 66.4%, P < 0.001). In contrast, both modalities demonstrated comparable sensitivity in identifying primary breast tumors (100% vs. 100%), regional lymph node metastases (85.4% vs. 81.4%, P = 0.388), and distant lymph node metastases (84.2% vs. 75.0%, P = 0.159). With respect to semiquantitative parameters, [68Ga]Ga-FAP-2286 PET/CT demonstrated significantly higher uptake in bone metastases than [18F]FDG PET/CT (SUVmax: 8.7 ± 3.9 vs. 6.7 ± 2.8, P = 0.002; TBR: 5.4 ± 2.2 vs. 3.8 ± 1.3, P < 0.001). However, for primary tumors, regional lymph nodes, distant lymph nodes, pulmonary metastases, and hepatic metastases, no statistically significant differences in SUVmax or TBR values were observed between the two tracers (all P > 0.05). [177Lu]Lu-FAP-2286 demonstrated sustained high tumor uptake up to 168h post-injection. In the four treated patients, the mean absorbed doses to tumor lesions were 0.21 ± 0.09, 0.27 ± 0.14, 0.14 ± 0.05, and 1.02 ± 0.30Gy/GBq, respectively. Notably, in one patient, the total absorbed dose for all tumor lesions reached 54.23Gy/GBq at 168h. No grade III or IV adverse events were observed, and three of four patients exhibited stable disease (SD) on follow-up. [68Ga]Ga-FAP-2286 appears to be a promising imaging agent for breast cancer, while [177Lu]Lu-FAP-2286 may represent a potential therapeutic option for patients with advanced disease.

Cancer is a non-communicable disease that is the leading cause of death in the world, including Indonesia. One of the main treatments for cancer is chemotherapy, which although effective, often causes severe side effects, one of which is fatigue. Fatigue in cancer patients not only affects the physical, but also emotional and mental. In dealing with this condition, resilience plays an important role. Resilience can help patients survive, adapt, and stay enthusiastic about undergoing treatment. This study is a quantitative study with a cross-sectional approach, using The Connor-Davidson Resilience Scale (CD-RISC) questionnaire on the resilience variable and the Fatigue Assessment Scale (FAS) questionnaire on the Fatigue variable. The sampling technique is non-probability sampling by consecutive sampling. The number of samples is 132 respondents in cancer patients undergoing chemotherapy at Baladhika Husada Hospital, Jember. Data analysis uses univariate analysis with the Spearman rank. The results of the study showed that respondents who had poor resilience and severe fatigue were 15 (11.4%), moderate resilience and moderate fatigue were 41 (31.1%), and good resilience and mild fatigue were 33 (25%). The results of the Spearman rank test analysis obtained a p value of 0.000 &lt;α (0.05) and the contingency value was equal to -0.465, meaning a moderate relationship with a negative correlation direction. There is a significant relationship between resilience and fatigue in cancer patients undergoing chemotherapy at Baladhika Husada Hospital, Jember.

The World Health Organization's survey indicates that cancer is the second leading cause of death globally. The identification of early markers and the early detection of asymptomatic tumors remain the most critical objectives for effective treatment and improved survival. Human blood sample analysis is a noninvasive technique used in patient care and cancer research. Currently, certain genes, gene products and tumor markers measured in blood are routinely used for diagnosis and monitoring. The thermoanalytical examination of the human blood plasma proteome is a promising new area, where blood sampling can be considered a type of liquid biopsy. Differential scanning calorimetry (DSC) directly measures the stability and decomposition of proteins, lipids, or nucleic acids during a controlled increase or decrease in temperature, allowing the study of individual substances in their native and denatured states. This thermoanalytical DSC curve of a biomolecule or biostructure is unique, like a fingerprint, and shows normal or pathomorphological changes under specific circumstances. Various clinical conditions (malignant melanoma, breast tumor, pancreatic tumor) showed unique but disease-specific DSC thermograms obtained from measurements of patients' blood plasma, which correlated with disease severity, progression, or response to treatment. Following further development, deconvolution analysis of blood plasma DSC curves raises the possibility of early diagnosis of cancerous or inflammatory conditions, disease monitoring, or testing the effectiveness of therapy used from a single drop of blood. Orv Hetil. 2026; 167(3): 98-108.

Stroke remains a leading cause of disability and death globally, with carotid stenosis as a major contributor. Carotid endarterectomy with patch angioplasty reduces restenosis risk, but current patch materials often lack biocompatibility and biodegradability. This study introduces a novel vascular patch composed of poly-L-lactic acid (PLLA) and chitosan, coated with heparin, designed to promote tissue integration and safe degradation. A true experimental in vivo study was conducted using 54 Wistar rats, divided into three groups: (1) PLLA scaffold (Group K1/K2), (2) PLLA-chitosan scaffold (Group P1/P3), and (3) PLLA-chitosan with heparin coating scaffold (Group P2/P4). Histological analyses at 14 and 56 days post-implantation evaluated inflammatory response, fibrous capsule formation, and angiogenesis. Statistical analysis included ANOVA, T-test, and Mann-Whitney U test (significance p < 0.05). At 14 days, inflammatory cell infiltration differed significantly among groups (p = 0.019), with the PLLA-chitosan patch showing the lowest inflammatory cell count. By 56 days, inflammation had subsided in all groups (p = 0.989). Initial fibrous capsule thickness at 14 days was higher in the heparin-coated group and differed significantly among groups (p = 0.019), but by 56 days all groups showed stable fibrous encapsulation with no significant differences (p = 0.916). All implants supported neovascularization, with evidence of new blood vessel formation (angiogenesis) around the patch materials. No excessive fibrous tissue formation or cytotoxic effects were observed in any group. The heparin-coated PLLA-chitosan patch displayed good biocompatibility, modulating inflammation, and supporting neovascularization. These findings suggest its potential as a vascular graft for large vessel reconstruction, though further long-term studies are needed.

Introduction: The prevalence of non-communicable disease is increasing world-wide; chronic kidney disease is one of them. The burden of kidney disease related mortality in working age group was not reported from Myanmar. Methods: A hospital based retrospective descriptive study was conducted in one selected public hospital in Yangon, Myanmar. The design focused on analyzing data from brought-in-deaths (BID) and hospital admission deaths (HAD) among the working age group (18-62 years) over a 10-year period; January 1, 2015 to December 31, 2024. All cases underwent postmortem examination done by a forensic surgeon for BID cases and a pathologist for HAD cases. And the cause of death was verified. Results: A total of 3,087 death cases were reviewed from hospital records; a quarter (744/3,087; 24.1%) was BID cases and two third (2,343/3,087; 75.9%) was HAD cases. Mean age was 44 years (SD ± 12). Gastrointestinal and hepatobiliary diseases were the most prevalent cause among all deaths, accounting for half of them (50.5%). The remaining cause of death in order of frequency were as follows: hypertension (37.1%), cardiac diseases (27.4%), hematological diseases (22%), tuberculosis (20%), renal diseases (16.2%), malignancy (15%), surgery related death (12.3%), chronic obstructive airway disease (COPD) (11%), HIV infection (10%), stroke (9%), autoimmune diseases (9%), accidents and injury (9%), diabetes mellitus (6%), and poisoning including suicide &amp; homicide (3%). Nearly 85% of cases had more than one disease. Of all deaths, communicable diseases (CDs) attributed 30%; and 46% were due to non-communicable diseases (NCDs). Among all deaths due to renal diseases, acute kidney injury (AKI) was noted in 10%; chronic kidney disease/end stage renal disease (CKD/ESRD) was seen in 90%. AKI was mainly associated with septicaemia and volume loss; septicemia led to septic shock multi-organ failure (acute respiratory distress syndrome (ARDS), and disseminated intravascular coagulation DIC). Those deaths with CKD/ESRD had co-morbid diseases like hypertension (90%), diabetes mellitus (10%), ischemic heart disease and heart failure (25%), cerebrovascular accidents (10%), COPD (10%), autoimmune diseases (10%) and chronic liver disease with portal hypertension (5%). Regarding the proportion of BID and HAD cases in renal disease related deaths, only one percent them was BID and almost all (99%) were HAD indicating they received in-patient-care. Conclusion: Number of death due to non-communicable diseases (NCDs) was higher than that of communicable diseases (NCDs) among working age group in 10 years retrospective study; kidney disease was sixth leading cause of death. Chronic kidney disease/ESRD attributed 90% of kidney disease related deaths and they had associated co-morbid diseases. Hypertension was the most common co-morbid disease. To reduce the kidney disease related morbidity and mortality in working age group, hospital in-patient-care was not adequate. We need to strengthen preventive measures, early detection and treatment of non-communicable diseases (hypertension, diabetes mellitus, CKD), health education and life style modification to delay/prevent the development of CKD. Management of CKD should be placed on the global/national public health agenda.

Background/Objectives: Coronary Artery Disease (CAD) is one of the leading causes of death in the United States. Although there is a plethora of studies about CAD, there remains a gap in the literature in examining the role of CAD in patients who undergo spine surgery. In this study, we examine the role of CAD in postoperative outcomes in adult patients who underwent surgery for degenerative scoliosis. Methods: The Scoliosis Research Society Database was queried for patients with degenerative scoliosis and divided into two cohorts: CAD and non-CAD. To minimize confounding bias, propensity score matching was done on comorbidities and patient demographics. Outcomes examined included: intraoperative complications, postoperative outcomes, and mortality rate. After matching, there were 139 patients in each group. Results: The CAD group had significantly higher rates of cardiac-related complications (5.8% vs. 0%, p = 0.012). No other intraoperative complications had significant differences between the groups. Interestingly, the non-CAD group had both a higher rate of returning to surgery (46.8% vs. 33.8%, p = 0.038) and antibiotic-related complications (5.8% vs. 0.7%, p = 0.042) respectively. There were no other differences regarding postoperative outcomes, including mortality. Conclusions: Our study found that aside from cardiac-related complications, the CAD group did not have any worse outcomes, and in some cases did better. These results are promising and may be due to more extensive preoperative screening and more risk aversion in patients with CAD. Our findings suggest that if spine surgeons exercise risk management for cardiac complications, CAD patients may benefit greatly from scoliosis surgery at no increased risk.

Autopsies have long been performed to determine the cause of death in the medical field. In fact, autopsies have significantly contributed to our understanding of neurological and psychiatric disorders. Patients and their families who wish to donate bodies for autopsy may have various expectations, such as contributing to the development of treatments for the diseases they experienced or facilitating the investigation of their causes. They may also hope that the removed and stored organs will be used effectively and appropriately by academic institutions and pharmaceutical companies, both in Japan and abroad. Accordingly, brain banks store samples that can be utilized for future medical research. The Japan Brain Bank Net (JBBN) was established to help fulfill this purpose. The network currently includes 19 institutions. In addition to storing and providing pathological tissue - functions traditionally associated with brain banks - JBBN also offers detailed and standardized neuropathological diagnoses. Currently, JBBN is working toward storing tissue suitable for emerging research methodologies, digitizing pathological images, applying artificial intelligence (AI) in neuropathological studies, and building a publicly accessible database. JBBN also aims to establish a permanent brain bank infrastructure to support the next generation of research.

Cancer is the leading cause of death in most developed nations. Although significant efforts have been made to develop targeted cancer chemotherapy drugs for decades, dosing of chemotherapy drugs is still limited by systematic toxic side effects. To reduce the toxicities of chemotherapy, we have designed a 3D printed biosponge adsorber that can capture the excess untrapped chemotherapy drugs in situ before they circulate throughout the body. Specifically, we focused on liver cancer because of the liver's proximity to the heart with a model drug, doxorubicin (Dox), a highly effective chemotherapy drug with severe cardiac failure risk. Our adsorbers were prepared by forming porous lattice scaffolds via 3D printing and then adding a thin drug (Dox)-adsorbing layer of sulfonated nanostructured block copolymer on the scaffolds. The porous lattices were designed to provide a large surface area for effective drug capture but not to impair the blood flow. The drug-adsorbing block of the polymer layer is polystyrenesulfonate (PSS), which strongly binds to Dox. Using these design parameters, we have successfully placed the adsorbers in the veins downstream of the liver, i.e., the hepatic veins and inferior vena cava (IVC) draining the liver, while the drug (Dox) was injected directly to the liver, mimicking the state-of-the-art, intra-arterial chemotherapy (IAC) procedure for liver cancer patients. Our adsorbers can capture a significant amount of the excess untrapped Dox in situ. The adsorbers can significantly reduce Dox accumulation in the heart (50%) and kidneys (36%) as well as in the surrounding bloodstream (25-45%). Cell viability studies using H9c2 cells confirmed that our adsorbers reduce Dox-induced cardiotoxicity. Additionally, the placement of the adsorbers neither severely impairs the blood flow nor significantly raises blood pressure in the adjacent veins. This confirms the feasibility of the in vivo adsorption approach. Our development poses a potential new route to minimize off-target chemotherapy toxicities and thus help people fight cancer by enabling high-dose locoregional chemotherapy.

The number of elderly people in Indonesia continues to increase, presenting significant challenges, particularly in the health sector. This includes a rising prevalence of degenerative diseases such as type 2 diabetes mellitus and cardiovascular disease. Older adults are highly vulnerable to imbalances in blood sugar levels, and elevated cholesterol is a major risk factor for cardiovascular disease, which remains a leading cause of death among the elderly. According to Pergemi (2022), the prevalence of diabetes, high cholesterol, and cardiovascular disease is notably high among this age group. This study aimed to examine the relationship between random blood sugar levels and cholesterol levels in elderly individuals. This was a descriptive correlational study using a cross-sectional approach. The sampling technique used was purposive sampling, with a total of 48 elderly respondents undergoing health checks in Jakarta. Data were collected from the results of blood sugar levels and cholesterol level tests. The data were analyzed using the Chi-Square test. The test result showed a p-value of 0.277, indicating no significant correlation between random blood sugar levels and cholesterol levels in the elderly. It is recommended that older adults regularly monitor their health, maintain a healthy lifestyle, and stay physically active.

Cardiovascular disease has become the leading cause of death. It is the common goal for researchers worldwide to develop small-diameter vascular grafts (SDVGs) which could meet clinical needs. In this study, PLGA@PCL core-shell structural fibrous SDVGs was fabricated by coaxial electrospinning process, and then the surface heparinization of the vascular material was carried out after H2N-PEG-NH2 fixed on sodium hydroxide-treated electro-spun PCL tubes. Finally, the long-term patency and tissue regeneration of the grafts were evaluated in vivo through the rabbit carotid artery replacement model. The results indicate that the heparin-modified PLGA@PCL core-shell structural fibrous SDVGs achieved long-term patency and the arrangement of collagen and elastin in the neointima was similar to the native vessel in the rabbits after 9 months. After 3 months postoperatively, endothelialization was almost complete, and vascular calcification was also observed. It can be concluded that surface heparinization is a feasible modification method for in situ tissue-engineered vascular grafts, and controlling the occurrence of vascular calcification is another important issue to be solved in the development of SDVGs, and it is also the focus of our next research work.

Cardiovascular disease has become the leading cause of death. It is the common goal for researchers worldwide to develop small-diameter vascular grafts (SDVGs) which could meet clinical needs. In this study, PLGA@PCL core-shell structural fibrous SDVGs was fabricated by coaxial electrospinning process, and then the surface heparinization of the vascular material was carried out after H2N-PEG-NH2 fixed on sodium hydroxide-treated electro-spun PCL tubes. Finally, the long-term patency and tissue regeneration of the grafts were evaluated in vivo through the rabbit carotid artery replacement model. The results indicate that the heparin-modified PLGA@PCL core-shell structural fibrous SDVGs achieved long-term patency and the arrangement of collagen and elastin in the neointima was similar to the native vessel in the rabbits after 9 months. After 3 months postoperatively, endothelialization was almost complete, and vascular calcification was also observed. It can be concluded that surface heparinization is a feasible modification method for in situ tissue-engineered vascular grafts, and controlling the occurrence of vascular calcification is another important issue to be solved in the development of SDVGs, and it is also the focus of our next research work.

Hypertensive disease remains one of the leading contributors to cardiovascular morbidity and mortality worldwide, with hyperlipidemia as a major metabolic comorbidity. There is a relative absence of long-term mortality trends that directly assess the co-occurrence of hypertension and hyperlipidemia. We analyzed mortality data from the CDC WONDER platform (1999-2023), including adults aged ≥65 years with hypertensive disorders I10-I15 and hyperlipidemia E78 (E78.0-78.5, E78.8, E78.9) as multiple causes of death. Age-adjusted mortality rates (AAMRs) and average annual percentage changes were calculated using Joinpoint regression, stratified by sex, race/ethnicity, urbanization, region, and age. A total of 960,024 deaths in the United States from 1999 to 2023 were identified. The AAMR per 100,000 ranged from 6.56 [95% confidence interval (CI), 6.29-6.83] in 1999 to 163 (95% CI, 162-164) in 2023. The highest AAMR was reported in 2021, at 164 (95% CI, 163-166). AAMRs were highest among non-Hispanic Black or African American patients. Overall, the mortality rates for both women and men increased steadily over the study period, with men consistently showing higher mortality rates than women. Mortality rates for both women and men increased steadily over the study period, with men showing higher mortality rates than women. Mortality rates from hypertension and hyperlipidemia together have escalated in the United States over the past 25 years. However, the death trends were unequal across demographics, which underscores the necessity for equitable access to medical services and integrated risk reduction to improve cardiometabolic outcomes.

Globally, liver cancer is the sixth most prevalent cancer type and the third leading cause of cancer-related deaths, making the need for improved treatment evident. We conducted a pan-cancer tissue microarray analysis to identify cancer types with upregulated ribosome biogenesis, potentially suitable for treatment with nucleolar-targeting compounds. Our screening identified liver cancer as a potential candidate. Gene expression analysis confirmed upregulation of nucleolar factors facilitating ribosome biogenesis that correlated with poor prognosis. In hepatocellular carcinoma (HCC) cell lines, constituting around 80% of liver cancer cases, we confirmed the upregulation of the nucleolar proteins Treacle, UBF, and Fibrillarin, involved in transcription and processing of ribosomal RNA (rRNA). Measurements of rRNA also confirmed increased nucleolar activity. We treated the HCC cell lines with nucleolar-targeting compounds and observed increased sensitivity in the HCC cell lines. Notably, nucleolar targeting compounds demonstrated a broader therapeutic window than that observed for Sorafenib, a clinically approved targeted therapy. Furthermore, we investigated how nucleolar factors change during HCC stages and found a progressive increase in Treacle and Fibrillarin in advanced stages of HCC. Our results demonstrate aberrant nucleolar activity in HCC and propose targeting ribosome biogenesis as a therapeutic strategy to improve HCC patient outcomes.

Venous thromboembolism (VTE) is the leading cause of preventable hospital deaths. Adults hospitalised with psychiatric illness vary in their risk of VTE, and therefore in their likelihood of benefiting from thromboprophylaxis. There is a paucity of evidence-based practice guidelines addressing VTE prophylaxis for this population despite recognition of additional VTE risk factors in this population. To develop an evidence-based guideline on VTE prophylaxis for patients hospitalised with psychiatric illness using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). An international, multidisciplinary, guideline panel including clinical experts, methodologists, and a patient partner was recruited by invitation. Panelists were selected based on methodological and clinical expertise on this subject. Panel members were diverse in geography (from Ireland, the United Kingdom, France, and Canada), expertise and gender. The panel was composed of four advanced specialist psychiatric pharmacists, four consultant haematologists, four consultant psychiatrists, one advanced nurse practitioner in psychiatry, one advanced nurse practitioner in anticoagulation, a methodologistwith expertise using GRADE, and a patient partner with lived experience of VTE. The panel prioritised two clinical questions and related population, interventions, outcomes, and secondary analyses according to their importance for patients. GRADE was used to assess certainty of evidence and to move from evidence to risk-stratified recommendations. The panel made three recommendations: a strong recommendation against parenteral pharmacological prophylaxis for patients at low risk of VTE (moderate-certainty evidence); a conditional recommendation in favour of parenteral pharmacological prophylaxis in high-risk patients (low-certainty evidence); and a strong recommendation against graduated compression stockings in patients at high risk of VTE with a contraindication to parenteral pharmacological prophylaxis (low-certainty evidence). Clinicians should not use parenteral pharmacological prophylaxis in adults hospitalised with psychiatric illness at low risk of VTE; and should consider using parenteral pharmacological prophylaxis for high-risk adults with no contraindications. Graduated compression stockings are not recommended in high-risk patients when parenteral pharmacological prophylaxis is contraindicated. These GRADE- based recommendations offer one of the first evidence-based practice guidelines for thromboprophylaxis decisions in psychiatric in-patient settings.

Full post-mortem examinations (conventional autopsies) are a valuable tool for understanding disease mechanisms but are commonly rare, especially in epidemiological research. This study aimed to (1) assess conventional autopsy implementation in the Hamburg City Health Study (HCHS), (2) identify factors associated with conventional autopsy performance, and (3) compare conventional autopsy findings with presumed (clinical) causes of death. We assessed the implementation of conventional autopsies and the collection of related data within the HCHS, a population-based cohort of 16,411 individuals aged 45-74, enrolled since 2016. Conventional autopsy data were obtained through death and autopsy certificates over an up to 7-year follow-up period (spring 2016 to spring 2023). Descriptive analyses were performed, including baseline characteristics and causes of death. During a median follow-up of 4.33years, 354 participants (2.3% of the cohort) died. Death certificates were available for 275 cases, and 23 individuals underwent conventional autopsy (autopsy rate: 6.5%). In 10 cases (43.5%), the conventional autopsy confirmed the hypothesized cause of death, while in four cases (17.4%), there was a discrepancy or ambiguity between the death certificate and conventional autopsy findings. In the remaining nine cases (39.1%), no evident causal chain could be established based on external examination alone, which constituted the reason for conventional autopsy. Factors associated with a higher likelihood of conventional autopsy included unknown or non-natural causes of death (as judicial autopsy order) and prolonged hospitalization prior to death. Conducting systematic conventional autopsies in large, population-based cohorts is feasible but presents logistical and ethical challenges. Conventional autopsies often confirmed clinical diagnoses. Still, relevant discrepancies and ambiguities remained, in which conventional autopsy findings added relevant information for crucial clarification. Incorporating conventional autopsy findings enhances the accuracy of mortality data and strengthens epidemiological outcome assessments.

Improving the efficacy of retreatment for locally recurrent nasopharyngeal carcinoma (rNPC) and extending patient survival are urgently required for the clinical prevention and treatment of NPC. This study explored the efficacy and safety of toripalimab in combination with concurrent chemoradiotherapy (CCRT) for the treatment of rNPC. This single-arm, Phase 2 trial included patients with rNPC who met the inclusion criteria as confirmed by pathology or imaging. The patients received toripalimab combined with CCRT. The primary end point was the objective response rate (ORR) of the patients. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile. Between April 2020 and September 2023, 40 patients with rNPC were recruited. The best response of ORR after radiotherapy was 87.5% (95% confidence interval [CI]: 72.0-95.0), with a DCR of 100%. The median PFS for rNPC was 18.1 months (95% CI, 15.2-28.8). The 1-year, 2-year, and 3-year PFS rates were 68.2%, 41.3%, and 15.5%, respectively. The median OS for rNPC was 28.3 months (95% CI, 18.6-Not Available [NA]). The 1-year, 2-year, and 3-year OS rates were 69.7%, 53.9%, 44.8%. The most common acute toxicities were hematological toxicities, including lymphopenia (100%) and anemia (92.5%), whereas the most common late toxicities were dry mouth (60.0%) and nasopharyngeal wall necrosis (40.0%). Fatal epistaxis was the cause of death in 22.5% of patients. Toripalimab plus CCRT demonstrates antitumor efficacy in rNPC. The observed 22.5% rate of fatal epistaxis indicates that its potential benefits must be carefully weighed against this serious treatment-related risk.

Stroke is a leading cause of death and disability, with survivors often facing upper extremity (UE) impairments. Mirror therapy (MT) can enhance motor function but is influenced by cognitive and emotional factors. Robot-assisted therapy (RT) has shown efficacy in restoring UE function. Robot-mirror therapy (RMT), which combines MT and RT, has been investigated in several trials, with some showing benefits while others reported limited effects. This meta-analysis aimed to evaluate RMT's effectiveness in improving UE function in stroke patients. We included RCTs involving RMT in adult stroke patients. Searches covered ten databases (Cochrane Library, Scopus, PubMed, Web of Science, Embase, CNKI, CINAHL, PEDro, ClinicalTrials.gov, WHO ICTRP) through October 2025, with a grey literature search. Two independent reviewers conducted study selection, data extraction, and quality assessment. The risk of bias and the certainty of the evidence were assessed using the Cochrane collaboration's tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline, respectively. Sixteen RCTs (n=736) were analyzed. RMT significantly improved UE motor function (Fugl-Meyer Assessment-Upper Extremity (FMA-UE); MD 7.52, 95% CI 4.16-10.87; P<.0001 and Wolf Motor Function Test; MD 5.13, 95% CI 2.33-7.92; P=.0003), distal UE motor function (FMA-UE (distal); MD 2.92, 95% CI 1.43-4.42; P=.0001), hand motor function (SMD 1.06, 95% CI 0.15-1.97; P=.02), hand muscle strength (grip strength; SMD 1.34, 95% CI 0.17-2.51; P=.02), activities of daily living (Modified Barthel Index; MD 7.80, 95% CI 4.15-11.45; P<.0001 and Functional Independence Measure; MD 4.73, 95% CI 0.30-9.15; P=.04), and quality of life (SMD 1.00, 95% CI 0.00-1.99; P=.05). Subgroup analysis showed better outcomes in older patients (≥55), shorter interventions (<18 hours), and trial length of 3-6 weeks. Moderate-quality evidence supports the effectiveness of RMT-based interventions for improving UE motor function and activities of daily living in stroke patients. Trial Registration PROSPERO CRD420251077740.